title: Preparation and First Preclinical Evaluation of [(18)F]FE@SNAP: A Potential PET Tracer for the Melanin-Concentrating Hormone Receptor-1 (MCHR1).
abstract: The melanin-concentrating hormone (MCH) system is a new target for the treatment of human disorders. Since the knowledge of the MCH system's involvement in a variety of pathologies (obesity, diabetes, and deregulation of metabolic feedback mechanism) is based on in vitro or preclinical studies, a suitable positron emission tomography (PET) tracer needs to be developed. We herein present the preparation and first preclinical evaluation of [(18)F]FE@SNAP - a new PET tracer for MCH receptor-1 (MCHR1). The synthesis was performed using a microfluidic device. Preclinical evaluation included binding affinity, plasma stability, plasma free fraction, stability against the cytochrome P-450 (CYP450) system using liver microsomes, stability against carboxyl-esterase, and methods to assess the penetration of the blood-brain barrier (BBB) such as logD analysis and immobilized artificial membrane (IAM) chromatography. Levels at 374 ± 202 MBq [(18)F]FE@SNAP were obtained after purification. The obtained K d value of [(18)F]FE@SNAP was 2.9 nM. [(18)F]FE@SNAP evinced high stability against carboxylesterase, CYP450 enzymes, and in human plasma. LogD (3.83) and IAM chromatography results (Pm=0.51) were in the same range as for known BBB-penetrating compounds. The synthesis of [(18)F]FE@SNAP was reliable and successful. Due to high binding affinity and stability, [(18)F]FE@SNAP is a promising tracer for MCHR1.
authors.affiliation: Radiochemistry and Biomarker Development Unit, Department of Nuclear Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. ; Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstraße 14, 1090 Vienna, Austria.
authors.forename: Cécile
authors.initials: C
authors.lastname: Philippe
authors.forename: Lukas
authors.initials: L
authors.lastname: Nics
authors.forename: Markus
authors.initials: M
authors.lastname: Zeilinger
authors.forename: Eva
authors.initials: E
authors.lastname: Schirmer
authors.forename: Helmut
authors.initials: H
authors.lastname: Spreitzer
authors.forename: Georgios
authors.initials: G
authors.lastname: Karanikas
authors.forename: Rupert
authors.initials: R
authors.lastname: Lanzenberger
authors.forename: Helmut
authors.initials: H
authors.lastname: Viernstein
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wadsak
authors.forename: Markus
authors.initials: M
authors.lastname: Mitterhauser
keywords: Fluorine-18; MCHR1; PET; Radioligand; SNAP-7941